First artificial human ovary created

Scientists have created the first artificial human ovary, an advance that provides a potentially powerful new means for conducting fertility research and could also yield infertility treatments for cancer patients.

The team of researchers at Brown University and Women & Infants Hospital has already used the lab-grown organ to mature human eggs.

"An ovary is composed of three main cell types, and this is the first time that anyone has created a 3-D tissue structure with triple cell line," said Sandra Carson, professor of obstetrics and gynecology at the Warren Alpert Medical School of Brown University and director of the Division of Reproductive Endocrinology and Infertility at Women & Infants Hospital.

Carson said that the ovary not only provides a living laboratory for investigating fundamental questions about how healthy ovaries work, but also can act as a testbed for seeing how problems, such as exposure to toxins or other chemicals, can disrupt egg maturation and health.

Clinically, the artificial ovary could play a role in preserving the fertility of women facing cancer treatment in the future, said Stephan Krotz, a Houston fertility doctor who is the paper’s lead author and a former fellow in Carson’s lab.

Immature eggs could be salvaged and frozen before the onset of chemotherapy or radiation, he said, and then matured outside the patient in the artificial ovary.

What makes the artificial ovary a functional tissue, rather than just a cell culture, is that it brings all three ovarian cell types into a 3-D arrangement similar to a real ovary in the body.

The means for making such compositions of cells was invented in the lab of Jeffrey Morgan, associate professor of medical science and engineering, who is a co-author of the paper. His so-called 3D Petri dishes are made of a moldable agarose gel that provides a nurturing template to encourage cells to assemble into specific shapes.

To create the ovary, the researchers formed honeycombs of theca cells, one of two key types in the ovary, donated by reproductive-age (25-46) patients at the hospital.

After the theca cells grew into the honeycomb shape, spherical clumps of donated granulosa cells were inserted into the holes of the honeycomb together with human egg cells, known as oocytes. In a couple days the theca cells enveloped the granulosa and eggs, mimicking a real ovary.

The big test, however, was whether the structure could function like an ovary — namely to mature eggs. In experiments the structure was able to nurture eggs from the "early antral follicle" stage to full maturity.

The innovation has been described in the Journal of Assisted Reproduction and Genetics.